Kinetic analyses of [123I]IBZM SPECT for quantification of striatal dopamine D2 receptor binding: a critical evaluation of the single-scan approach.

Background: Dopamine-D2 receptor imaging with single-photon emission computed tomography (SPECT) and [(123)I]IBZM is of great interest for basic and applied neurosciences. However, the use of kinetic analyses for quantification of dynamic [(123)I]IBZM SPECT and the validity of the commonly employed single-scan pseudo-equilibrium analysis (PsEA) have not been appropriately investigated. The present study addresses these shortcomings.
Methods: Ten movement disorder patients underwent dynamic SPECT (142 min) after single-bolus [(123)I]IBZM injection. Kinetic analyses comprise: simplified reference tissue model (SRTM), multi-linear reference tissue model (MRTM), their two-parameter versions (SRTM2/MRTM2) and non-invasive graphical analysis (NIGA). Simplified single-scan analyses were performed at peak time of specific binding (peak-equilibrium analysis, PEA) and during pseudo-equilibrium (PsEA).
Results: SRTM and MRTM are compromised by the high noise level of dynamic SPECT. SRTM2 and MRTM2 yielded reliable binding potential estimates that agreed excellently (mean difference=-0.1+/-1.0%, R(2)>0.99). Concordance between SRTM/MRTM and SRTM2/MRTM2 was high in cases in which SRTM/MRTM provided reliable results (SRTM2 or MRTM2 vs. SRTM: 3.7+/-5.0%, R(2)=0.88). NIGA was affected by a negative bias (-9.1+/-6.3%, R(2)=0.75; MRTM2 as reference) or high variability (-1.2+/-7.4%, R(2)=0.71) for analyses without and with inclusion of the k(2)'-term, respectively. PsEA showed a positive bias and low correlation in comparison with SRTM2/MRTM2 (7.6+/-10.8%, R(2)=0.59), which was considerably improved for PEA (-2.7+/-7.6%, R(2)=0.72). MRTM2 provided parametric images with minimal bias suited for voxel-wise statistical analyses.
Conclusions: MRTM2 and SRTM2 can be reliably applied to dynamic [(123)I]IBZM SPECT. PEA is a suitable method for clinical routine, while our results discourage the use of PsEA (current clinical standard).